The Merck BioManufacturing Network, which is composed of two Merck business units—Diosynth Biotechnology and MSD Biologics—builds in QbD in biologics development and manufacture by way of high level of process understanding.
As Stephen Taylor, commercial director of MSD Biologics, explained, “during process development and laboratory process characterization (LPC) studies, the aim is to acquire a good understanding of each unit operation and define operating windows, to ensure acceptable and consistent product quality.
“If a high degree of process understanding is gained, and the process is consistently operated within the defined windows, then theoretically there should be less need to incorporate PAT.” According to Taylor, this approach brings operational and delivery benefits to clients by enabling a relatively high throughput of different products.
PAT is also being used in process development and selected manufacturing campaigns at Merck. “During a typical fermentation, critical quality parameters such as pH, temperature, CO2 evolution, O2 uptake rate, and respiratory quotient are monitored in real time using probes and in-line mass spec analysis,” Taylor commented. PAT has been implemented during downstream processing, though to a lesser extent “where real-time monitoring has been used to determine when process steps have progressed to an optimal level,” he added.
CMC Icos Biologics has integrated analytical characterization of the protein produced during the clonal selection phase of cell-line development with its CHEF-1® expression platform, focusing on selection of clones producing the highest quality product in addition to selecting for productivity and viability.
Jenifer L. Wheat, vp of business development, said that “ensuring choice of a clone expressing protein that matches the specifically desired analytical profile is critical for second-generation processes and biosimilar development. Monoclonality is also assured through imaging of colony outgrowth with Genetix’ CloneSelect, providing higher confidence levels in clonality than traditional limiting dilution cloning.”
Meridian Life Science is actively evaluating and implementing PAT initiatives. Design control, environmental monitoring, process yield improvements, CAPA streamlining, risk management, and process mapping are a few of the initiatives being implemented.
“These processes are helping Meridian increase our competitiveness and fully meet the needs of our customers in domestic and international markets,” commented Alan Rich, director of regulatory affairs and QA/QC. “They are allowing Meridian to shorten lead times for new product releases, reduce costs, minimize headcount, improve quality, and reduce scrap.”